AMPK and Neuropeptides are Invloved in Appetite Control

Hormones that control food consumption are involved with AMPK. This is further evidence that AMPK is important in the regulation of appetite. The activity of AMPK and the flux of fatty acid metabolism in the brain is involved in whole-body energy balance by regulation caloric intake. Leptin decreases food intake and ghrelin increases food intake.

Leptin inactivates AMPK. The rats were fasted for 12 hours and then were given 1.1mg/kg of leptin or saline. Their hypothalami were removed and analyzed at various time points.Figure 13 shows that leptin decreased AMPK activity. At 40 minutes there was no change in AMPK activity. At 60 minutes after the injection, there was a 25-30% decrease in AMPK activity that gradually returned to control levels in about 300 minutes. Western blot analysis on the same tissues showed a decreased amount of active ACC and AMPK. The decreased activity of AMPK caused the decreased activity of ACC. Figure 14 is the decreased activity of ACC and figure 15 shows the decreased active AMPK levels. Leptin inactivates AMPK which then inactivates ACC. These results further support the hypothesis that decreased AMPK is associated with lipid metabolism in the hypothalamus.

Diagram 5. Leptin decreases AMPK and ACC in the hypothalamus.

Ghrelin regulates AMPK in the hypothalamus. Mice were injected with 30nmoles of ghrelin and their hypothalamic tissue was analyzed. Along with the activation of AMPK (figure 16 and 18), there was an increased amount of phosphorylated ACC (figure 17). As mentioned earlier, AMPK activates ACC. As expected, the effects of ghrelin on AMPK are opposite to the effects of leptin.

Diagram 6. Ghrelin increases AMPK and ACC activity in the hypothalamus.

Leptin and ghrelin were chosen to prove that AMPK is directly involved in the regulation of food intake. Since it is established that these neuropoptides play a central role in appetite and thus obesity, connecting them directly to AMPK proves that AMPK is also central to the regulation of food intake.

Figure 12. The studies by Andersson 2004 were done in male Winstar rats. Injections of saline, leptin or ghrelin were given after a 12 hour fast and later the hypothalami were surgically extracted.

Figure 13. Leptin injection caused a time-dependent decrease in AMPK activity in the rat hypothalamus (Andersson 2004).

Figure 14. The level of phosphorylated, active, ACC in hypothalamus decreases with leptin injection (Andersson 2004).

Figure 15. The level of phosphorylated, active, AMPK in the hypothalamus decreases with leptin injection (Andersson 2004).

Figure 16. Ghrelin injection caused a time-dependent increase in AMPK activity in the rat hypothalamus (Andersson 2004).

Figure 17. The level of phosphorylated, active, ACC in the hypothalamus increases with ghrelin injection (Andersson 2004).

Figure 18. The level of phosphorylated, active, AMPK in the hypothalamus increases with ghrelin injection (Andersson 2004).